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Goncalves B.P.,London School of Hygiene and Tropical Medicine | Walker P.G.,Imperial College London | Cairns M.,London School of Hygiene and Tropical Medicine | Tiono A.B.,Center National Of Recherche Et Of Formation Sur Le Paludisme | And 2 more authors.
Trends in Parasitology | Year: 2017

Community chemotherapy campaigns to reduce malaria transmission often exclude pregnant women due to safety concerns related to the drugs. However, pregnant women might represent an important source of human-to-mosquito infection due to frequent parasite carriage with higher densities of parasites (often detectable by microscopy), attractiveness to mosquitoes, and modified sleeping behaviour. Accumulating evidence of the safety of artemisinin-based combination therapies for the treatment of malaria during gestation suggests that malaria elimination programmes should reconsider this exclusion. Including pregnant women will increase intervention coverage and impact, and may thereby accelerate progress towards the desired endpoint (e.g., elimination) or increase the chances of success. Studies assessing infectiousness of pregnant women and gametocyte dynamics during different trimesters of pregnancy will be valuable to support the planning of community treatment campaigns. The World Health Organization recently recommended mass drug administration (MDA) to accelerate Plasmodium falciparum elimination efforts. Previous MDA campaigns often excluded pregnant women due to concerns related to potential teratogenic effects of the drugs being administered.There is growing epidemiological and entomological evidence that pregnant women might represent an important source of mosquito malaria infection due to their frequent high-density parasite carriage, attractiveness to mosquitoes, and behaviour.New evidence of the safety of artemisinin-based combination therapy administration during gestation suggests that both MDA coverage and maternal health could be improved during such campaigns using community-based diagnosis of high-density infection in pregnant and potentially pregnant women. © 2017 Elsevier Ltd.


Guelbeogo W.M.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Sagnon N.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Liu F.,University of Notre Dame | Besansky N.J.,University of Notre Dame | Costantini C.,IRD Montpellier
Malaria Journal | Year: 2014

Background: In Burkina Faso, two chromosomal forms of the malaria vector Anopheles funestus, Folonzo and Kiribina, are distinguished by contrasting frequencies of shared polymorphic chromosomal inversions. Sympatric and synchronous populations of Folonzo and Kiribina mate assortatively, as indicated by a significant deficit of heterokaryotypes, and genetic associations among inversions on independently segregating chromosome arms. The present study aimed to assess, by intensive longitudinal sampling, whether sympatric Folonzo and Kiribina populations are characterized by behavioural differences in key malaria vectorial parameters. Methods. The study was conducted in two adjacent villages near Ouagadougou, in the dry savanna of central Burkina Faso. Mosquito adult resting behaviour of both forms was compared based on parallel indoor/outdoor collections across six breeding seasons; 8,235 fully karyotyped samples of half-gravid females were analysed in total. Additionally, indoor/outdoor human biting behaviour, host selection, and Plasmodium falciparum sporozoite rate was assessed and compared between chromosomal forms. Results: The Kiribina form was numerically predominant in the area. However, the Folonzo form was significantly over-represented in indoor resting collections and showed stronger post-prandial endophily, while Kiribina predominated outdoors. Neither form was statistically distinguishable in human biting behaviour, and both were more likely to seek human blood meals indoors than outside. The human blood index and sporozoite rate were comparably high in both chromosomal forms in indoor collections (>89% and >8%, respectively). Conclusions: Both Kiribina and Folonzo chromosomal forms are formidable malaria vectors in Burkina Faso. However, the significantly greater tendency for the Kiribina form to rest outdoors despite its pronounced anthropophily suggests that uniform exposure of the overall An. funestus population to indoor-based vector control tools cannot be expected; Kiribina is more likely to evade indoor interventions and escape unharmed outdoors, reducing the efficacy of malaria control. Accordingly, more efficient methods to detect Kiribina and Folonzo, and a more complete understanding of their distribution and behaviour in Africa are advocated. © 2014 Guelbeogo et al.; licensee BioMed Central Ltd.


Crawford J.E.,Cornell University | Guelbeogo W.M.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Sanou A.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Traore A.,Center National Of Recherche Et Of Formation Sur Le Paludisme | And 4 more authors.
PLoS ONE | Year: 2010

Background: Anopheles funestus is one of the primary vectors of human malaria, which causes a million deaths each year in sub-Saharan Africa. Few scientific resources are available to facilitate studies of this mosquito species and relatively little is known about its basic biology and evolution, making development and implementation of novel disease control efforts more difficult. The An. funestus genome has not been sequenced, so in order to facilitate genome-scale experimental biology, we have sequenced the adult female transcriptome of An. funestus from a newly founded colony in Burkina Faso, West Africa, using the Illumina GAIIx next generation sequencing platform. Methodology/Principal Findings: We assembled short Illumina reads de novo using a novel approach involving iterative de novo assemblies and ''target-based'' contig clustering. We then selected a conservative set of 15,527 contigs through comparisons to four Dipteran transcriptomes as well as multiple functional and conserved protein domain databases. Comparison to the Anopheles gambiae immune system identified 339 contigs as putative immune genes, thus identifying a large portion of the immune system that can form the basis for subsequent studies of this important malaria vector. We identified 5,434 1:1 orthologues between An. funestus and An. gambiae and found that among these 1:1 orthologues, the protein sequence of those with putative immune function were significantly more diverged than the transcriptome as a whole. Short read alignments to the contig set revealed almost 367,000 genetic polymorphisms segregating in the An. funestus colony and demonstrated the utility of the assembled transcriptome for use in RNA-seq based measurements of gene expression. Conclusions/Significance: We developed a pipeline that makes de novo transcriptome sequencing possible in virtually any organism at a very reasonable cost ($6,300 in sequencing costs in our case). We anticipate that our approach could be used to develop genomic resources in a diversity of systems for which full genome sequence is currently unavailable. Our An. funestus contig set and analytical results provide a valuable resource for future studies in this non-model, but epidemiologically critical, vector insect. © 2010 Crawford et al.


Okell L.C.,Imperial College London | Bousema T.,London School of Hygiene and Tropical Medicine | Bousema T.,Radboud University Nijmegen | Griffin J.T.,Imperial College London | And 3 more authors.
Nature Communications | Year: 2012

Malaria parasite prevalence in endemic populations is an essential indicator for monitoring the progress of malaria control, and has traditionally been assessed by microscopy. However, surveys increasingly use sensitive molecular methods that detect higher numbers of infected individuals, questioning our understanding of the true infection burden and resources required to reduce it. Here we analyse a series of data sets to characterize the distribution and epidemiological factors associated with low-density, submicroscopic infections. We show that submicroscopic parasite carriage is common in adults, in low-endemic settings and in chronic infections. We find a strong, non-linear relationship between microscopy and PCR prevalence in population surveys (n=106), and provide a tool to relate these measures. When transmission reaches very low levels, submicroscopic carriers are estimated to be the source of 20-50% of all human-to-mosquito transmissions. Our findings challenge the idea that individuals with little previous malaria exposure have insufficient immunity to control parasitaemia and suggest a role for molecular screening. © 2012 Macmillan Publishers Limited.


Churcher T.S.,Imperial College London | Bousema T.,Radboud University Nijmegen | Bousema T.,London School of Hygiene and Tropical Medicine | Walker M.,Imperial College London | And 4 more authors.
eLife | Year: 2013

Transmission reduction is a key component of global efforts to control and eliminate malaria; yet, it is unclear how the density of transmission stages (gametocytes) influences infection (proportion of mosquitoes infected). Human to mosquito transmission was assessed using 171 direct mosquito feeding assays conducted in Burkina Faso and Kenya. Plasmodium falciparum infects Anopheles gambiae efficiently at low densities (4% mosquitoes at 1/μl blood), although substantially more (>200/μl) are required to increase infection further. In a site in Burkina Faso, children harbour more gametocytes than adults though the non-linear relationship between gametocyte density and mosquito infection means that (per person) they only contribute slightly more to transmission. This method can be used to determine the reservoir of infection in different endemic settings. Interventions reducing gametocyte density need to be highly effective in order to halt human-mosquito transmission, although their use can be optimised by targeting those contributing the most to transmission. © Churcher et al.


Pamba A.,Glaxosmithkline | Richardson N.D.,Magenta Communications Ltd. | Carter N.,Glaxosmithkline | Duparc S.,Medicines for Malaria Venture | And 3 more authors.
Blood | Year: 2012

Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68MandN126D. Drug-induced acutehemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735. © 2012 by The American Society of Hematology.


Gneme A.,University of Ouagadougou | Guelbeogo W.M.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Riehle M.M.,University of Minnesota | Tiono A.B.,Center National Of Recherche Et Of Formation Sur Le Paludisme | And 5 more authors.
Malaria Journal | Year: 2013

Background: Malaria can be caused by five Plasmodium species. Due to their higher prevalence, much of the research concentrates on Plasmodium falciparum and Plasmodium vivax. In Burkina Faso, where P. falciparum co-exists with Plasmodium malariae and Plasmodium ovale, there is not much data about the prevalence of the latter two species across human population. Moreover, interactions between co-infecting Plasmodium species are not documented. The aim of the current research is to determine species-specific prevalence and temporal distribution. The potential interactions between co-infecting Plasmodium species amongst the child-aged population in Burkina Faso are also discussed. Methods. The study took place in the Sudanese savannah zone in Burkina Faso in a rural village, Laye. Surveys were conducted during the wet season across four years, 2007 to 2010. Volunteers aged three to 15 years with parental signed consent were enrolled. Ten children per week were screened for any history of pain, fever. Parasitological data were obtained by blood slide processing. Results: Three sympatric Plasmodium species were recorded during this study with an average prevalence of 70.7%. Species temporal distribution showed an increase of P. malariae parasite prevalence from 0.9% in 2007 to 13.2% in 2010. Within a season, P. falciparum occurred in the overall study period while P. malariae and P. ovale were highly prevalent after the rainy part of this period. Species-specific infection analysis showed that in a comparison of mono-infections, P. malariae gametocyte prevalence and median density were higher than those of P. falciparum (88.9% vs 34.5% and 124.0 vs 40.0 gametocytes/μl, respectively). Likewise, in P. falciparum co-infections with P. malariae or P. ovale, gametocyte prevalence was also higher than in P. falciparum mono-infection. However, in P. falciparum mixed infection with P. malariae, P. falciparum gametocyte prevalence and median density as well as asexual form density decreased compared to P. falciparum mono-infection while for P. malariae mono-infection, only asexual form density significantly vary. Conclusion: These data revealed high gametocyte prevalence in other Plasmodium species than P. falciparum with a significant variation of P. malariae gametocyte carriers and gametocyte density across years. Molecular tools and entomological studies are needed to highly assess species-specific contribution to malaria transmission. © 2013 Gnémé et al.; licensee BioMed Central Ltd.


Badolo A.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Badolo A.,University of Ouagadougou | Traore A.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Jones C.M.,Vector Group | And 5 more authors.
Malaria Journal | Year: 2012

Background and methods. A longitudinal Anopheles gambiae s.l. insecticide-resistance monitoring programme was established in four sentinel sites in Burkina Faso. For three years, between 2008 and 2010, WHO diagnostic dose assays were used to measure the prevalence of resistance to all the major classes of insecticides at the beginning and end of the malaria transmission season. Species identification and genotyping for target site mutations was also performed and the sporozoite rate in adults determined. Results: At the onset of the study, resistance to DDT and pyrethroids was already prevalent in An. gambiae s.l. from the south-west of the country but mosquitoes from the two sites in central Burkina Faso were largely susceptible. Within three years, DDT and permethrin resistance was established in all four sites. Carbamate and organophosphate resistance remains relatively rare and largely confined to the south-western areas although a small number of bendiocarb survivors were found in all sites by the final round of monitoring. The ace-1 R target site resistance allele was present in all localities and its frequency exceeded 20% in 2010 in two of the sites. The frequency of the 1014F kdr mutation increased throughout the three years and by 2010, the frequency of 1014F in all sites combined was 0.02 in Anopheles arabiensis, 0.56 in An. gambiae M form and 0.96 in An. gambiae S form. This frequency did not differ significantly between the sites. The 1014S kdr allele was only found in An. arabiensis but its frequency increased significantly throughout the study (P=0.0003) and in 2010 the 1014S allele frequency was 0.08 in An. arabiensis. Maximum sporozoite rates (12%) were observed in Soumousso in 2009 and the difference between sites is significant for each year. Conclusion: Pyrethroid and DDT resistance is now established in An. gambiae s.l. throughout Burkina Faso. Results from diagnostic dose assays are highly variable within and between rounds of testing, and hence it is important that resistance monitoring is carried out on more than one occasion before decisions on insecticide procurement for vector control are made. The presence of 1014S in An. gambiae s.l., in addition to 1014F, is not unexpected given the recent report of 1014S in Benin but highlights the importance of monitoring for both mutations throughout the continent. Future research must now focus on the impact that this resistance is having on malaria control in Burkina Faso. © 2012Badolo et al.; licensee BioMed Central Ltd.


Tiono A.B.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Sirima S.B.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Hamed K.,Novartis
Malaria Journal | Year: 2013

Background: The Fulani ethnic group is known to have a lower susceptibility to Plasmodium falciparum infection than the Mossi. Methods. This commentary describes data from a recent cluster-randomized trial of community-wide screening and treatment of asymptomatic carriers of P. falciparum in 18 villages in Saponé, Burkina Faso. Results: The Fulani groups had a lower proportion of asymptomatic carriers at any occasion, a lower density of asexual forms and gametocytes of P. falciparum at baseline, and, in children under five years of age, lower rates of symptomatic malaria episodes per person-year than the Mossi. Discussion and conclusion. These data confirm previously reported differences in P. falciparum susceptibility between Fulani and Mossi. © 2013 Tiono et al.; licensee BioMed Central Ltd.


Bouchet N.,University of Tours | Bouchet N.,Center National Of Recherche Et Of Formation Sur Le Paludisme | Jaillet J.,University of Tours | Gabant G.,CNRS Center for Molecular Biophysics | And 4 more authors.
Nucleic Acids Research | Year: 2014

Genomic plasticity mediated by transposable elements can have a dramatic impact on genome integrity. To minimize its genotoxic effects, it is tightly regulated either by intrinsic mechanisms (linked to the element itself) or by host-mediated mechanisms. Using mass spectrometry, we show here for the first time that MOS1, the transposase driving the mobility of the mariner Mos1 element, is phosphorylated. We also show that the transposition activity of MOS1 is downregulated by protein kinase AMP cyclic-dependent phosphorylation at S170, which renders the transposase unable to promote Mos1 transposition. One step in the transposition cycle, the assembly of the paired-end complex, is specifically inhibited. At the cellular level, we provide evidence that phosphorylation at S170 prevents the active transport of the transposase into the nucleus. Our data suggest that protein kinase AMP cyclic-dependent phosphorylation may play a double role in the early stages of genome invasion by mariner elements. © 2013 The Author(s).

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